title: Chronic lymphocytic leukemia disease progression is accelerated by APRIL-TACI interaction in the TCL1 transgenic mouse model.
abstract: Although in vitro studies pointed to the tumor necrosis factor family member APRIL (a proliferation-inducing ligand) in mediating survival of chronic lymphocytic leukemia (CLL) cells, clear evidence for a role in leukemogenesis and progression in CLL is lacking. APRIL significantly prolonged in vitro survival of CD5(+)B220(dull) leukemic cells derived from the murine Eμ-TCL1-Tg (TCL1-Tg [transgenic]) model for CLL. APRIL-TCL1 double-Tg mice showed a significantly earlier onset of leukemia and disruption of splenic architecture, and survival was significantly reduced. Interestingly, clonal evolution of CD5(+)B220(dull) cells (judged by BCR clonality) did not seem to be accelerated by APRIL; both mouse strains were oligoclonal at 4 months. Although APRIL binds different receptors, APRIL-mediated leukemic cell survival depended on tumor necrosis factor receptor superfamily member 13B (TACI) ligation. These findings indicate that APRIL has an important role in CLL and that the APRIL-TACI interaction might be a selective novel therapeutic target for human CLL.
authors.affiliation: Laboratory of Experimental Oncology and Radiobiology.
authors.forename: Valeria
authors.initials: V
authors.lastname: Lascano
authors.forename: Marco
authors.initials: M
authors.lastname: Guadagnoli
authors.forename: Jan G
authors.initials: JG
authors.lastname: Schot
authors.forename: Dieuwertje M
authors.initials: DM
authors.lastname: Luijks
authors.forename: Jeroen E J
authors.initials: JE
authors.lastname: Guikema
authors.forename: Katherine
authors.initials: K
authors.lastname: Cameron
authors.forename: Michael
authors.initials: M
authors.lastname: Hahne
authors.forename: Steven
authors.initials: S
authors.lastname: Pals
authors.forename: Erik
authors.initials: E
authors.lastname: Slinger
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Kipps
authors.forename: Marinus H J
authors.initials: MH
authors.lastname: van Oers
authors.forename: Eric
authors.initials: E
authors.lastname: Eldering
authors.forename: Jan Paul
authors.initials: JP
authors.lastname: Medema
authors.forename: Arnon P
authors.initials: AP
authors.lastname: Kater
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D018450:Disease Progression; D057809:HEK293 Cells; D006801:Humans; D053208:Kaplan-Meier Estimate; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation; D011485:Protein Binding; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D053303:Transmembrane Activator and CAML Interactor Protein / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13 / Q000235:genetics / Q000378:metabolism*
chemical_list: D011518:Proto-Oncogene Proteins; C490393:Tcl1 protein, mouse; C486361:Tnfrsf13b protein, mouse; D053303:Transmembrane Activator and CAML Interactor Protein; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13